This is an open-label pilot study which is evaluating the effectiveness of IVIG as measured by in vitro steroid responsiveness, improved pulmonary function, and oral steroid reduction in severe steroid dependent asthmatics. We have enrolled 12 patients with steroid dependent asthma thus far. Of the 12 enrolled, 11 patients have successfully completed the study, 1 patient completed the study but her data will not be analyzed due to the diagnosis of a neutrophil defect being made after she was enrolled into the study. This neutrophil defect resulted in her developing recurrent pneumonias with pseudomonas and staph species. The recurrent lung infections made it difficult to determine the effect of IVIG on her lung function. All patients enrolled been were adolescents or young adults with an age range of 14 to 21 years (15.5+/-0.8 yrs). There were 5 males and 6 females. Four patients were African American, 1 patient Hispanic, and 6 were Caucasian. Six months of IVIG therapy resulted in >70% reduction in oral GC dose (34+/-8 pre- vs. 9+/-3 mg/d post-IVIG; p=0.01), decreased the number of prednisone bursts (2.6+/-0.5 vs. 1.1+/-0.4; p=0.04) and hospitalizations (3.0+/-.3 vs. 0.6+/-0.3; p=0.001) compared to 6 the months prior to entry. PEFR and FEV1values remained unchanged during the study despite the reductions in oral GC. IVIG resulted in improved GCR binding affinity (baseline Kd 38+/-5, 3 mo Kd 22+/-3, 6 mo Kd 21+/-3 nM). IVIG also caused a dose dependent suppression of lymphocyte stimulation with the combination of IVIG and GC resulting in greater suppression than either alone. We had two serious adverse events associated with IVIG which resulted in hospitalization- severe headache and anaphylaxis. Subject (WR) was enrolled in October 1996, and per protocol, received intravenous gamma globulin (IVIG) at a dose of 2 grams/kg of body weight. He tolerated the infusion without incident, but developed severe headache, nausea and lethargy 2 days post infusion. He was admitted to the Pediatric Special Care (PSC) Unit for observation and by the second day, his symptoms had resolved. The association to the study drug (IVIG) was considered likely. Due to the above reaction, WR received pre-treatment with hydrocortisone and diphenhydramine and his infusions were divided over two days. With the above changes, WR tolerated subsequent infusions without problems. Subject (JV) was enrolled in June 1997, and per protocol, received intravenous gamma globulin (IVIG) at a dose of 2 grams/kg of body weight. JV had tolerated the infusions without difficulty until October 13, 1997 (infusion #5) when he developed anaphylaxis. He had received approximately 70 gm out of a total of 90 gm of Gamimune-N when he developed facial "tingling", total body flushing, and generalized urticaria. He also felt "light headed" and nauseated. The infusion was immediately discontinued, his blood pressure was measured and noted to have fallen from 135/72 pre-infusion to 91/44. He was given 50 mg of Benadryl, and 100 mg of hydrocortisone intravenously. Upon my arrival, JV appeared "flushed" with urticaria over his upper body and face. He also had eyelid edema but was in no distress. No stridor or wheezing heard and he had good air entry. Oxygen was administered at 3 LPM and he was transferred to the Pediatric Special Care Unit where he received 0.3 cc epinephrine subcutaneously, and normal saline at 200 cc/hr intravenously. Over the next couple hours, JV's blood pressure improved, the urticaria resolved, and he was discharged to the outpatient department. The following day, he received his second infusion of IVIG (90 gm) over 6 hours without incident. The association to the study drug (IVIG) was considered likely. Due to the above reaction, JV received pre-treatment with hydrocortisone and diphenhydramine and the rate of his infusions were slowed. With the above changes, JV tolerated his subsequent infusions without incident.